Serine proteases of the prostate have potentially important roles in the biology of prostatic diseases. Prostate specific antigen (PSA), a member of the tissue kallikrein family of serine proteases, may regulate cellular growth by cleaving insulin growth factor-binding proteins (IGFBP's). This is significant especially since men with elevated IGF levels have recently been shown to have a 4-fold increase risk in the development of prostate cancer. Men with benign prostatic hyperplasia (BPH) also have abnormal progressive growth of the prostate gland. Whether IGF or other growth factors are involved in these processes is an intriguing question worth investigation. PSA has also been shown to elicit a bradykinin response by smooth muscle Cells when pre-incubated with seminal plasma. Because bradykinin stimulates inflammatory response, there may be a potential role of PSA in the pathogenesis of prostatitis. Our hypothesis therefore, is that PSA, and other serine proteases of the prostate, may be involved in the development of prostatic diseases such as BPH, prostatitis, and prostate cancer. We therefore, propose to study the potential pathogenic mechanisms of PSA, hK2 (another prostate specific serine protease) and other serine proteases recently isolated from the prostate.